PMID- 26059948
OWN - NLM
STAT- MEDLINE
DCOM- 20151027
LR  - 20220317
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 126
IP  - 6
DP  - 2015 Aug 6
TI  - Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated 
      safety and efficacy results.
PG  - 739-45
LID - 10.1182/blood-2015-03-635326 [doi]
AB  - Ibrutinib, an oral inhibitor of Bruton tyrosine kinase, is approved for patients 
      with mantle cell lymphoma (MCL) who have received one prior therapy. We report 
      the updated safety and efficacy results from the multicenter, open-label phase 2 
      registration trial of ibrutinib (median 26.7-month follow-up). Patients (N = 111) 
      received oral ibrutinib 560 mg once daily, and those with stable disease or 
      better could enter a long-term extension study. The primary end point was overall 
      response rate (ORR). The median patient age was 68 years (range, 40-84), with a 
      median of 3 prior therapies (range, 1-5). The median treatment duration was 8.3 
      months; 46% of patients were treated for >12 months, and 22% were treated for >/=2 
      years. The ORR was 67% (23% complete response), with a median duration of 
      response of 17.5 months. The 24-month progression-free survival and overall 
      survival rates were 31% (95% confidence interval [CI], 22.3-40.4) and 47% (95% 
      CI, 37.1-56.9), respectively. The most common adverse events (AEs) in >30% of 
      patients included diarrhea (54%), fatigue (50%), nausea (33%), and dyspnea (32%). 
      The most frequent grade >/=3 infections included pneumonia (8%), urinary tract 
      infection (4%), and cellulitis (3%). Grade >/=3 bleeding events in >/=2% of patients 
      were hematuria (2%) and subdural hematoma (2%). Common all-grade hematologic AEs 
      were thrombocytopenia (22%), neutropenia (19%), and anemia (18%). The prevalence 
      of infection, diarrhea, and bleeding was highest for the first 6 months of 
      therapy and less thereafter. With longer follow-up, ibrutinib continues to 
      demonstrate durable responses and favorable safety in relapsed/refractory MCL. 
      The trial is registered to www.ClinicalTrials.gov as #NCT01236391.
CI  - (c) 2015 by The American Society of Hematology.
FAU - Wang, Michael L
AU  - Wang ML
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX;
FAU - Blum, Kristie A
AU  - Blum KA
AD  - Ohio State University Comprehensive Cancer Center, Columbus, OH;
FAU - Martin, Peter
AU  - Martin P
AD  - Weill Cornell Medical College, New York, NY;
FAU - Goy, Andre
AU  - Goy A
AD  - John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, 
      NJ;
FAU - Auer, Rebecca
AU  - Auer R
AD  - Barts Health National Health Service (NHS) Trust, London, United Kingdom;
FAU - Kahl, Brad S
AU  - Kahl BS
AD  - University of Wisconsin School of Medicine and Public Health, Madison, WI;
FAU - Jurczak, Wojciech
AU  - Jurczak W
AD  - Jagiellonian University, Krakow, Poland;
FAU - Advani, Ranjana H
AU  - Advani RH
AD  - Stanford University Medical Center, Stanford, CA;
FAU - Romaguera, Jorge E
AU  - Romaguera JE
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX;
FAU - Williams, Michael E
AU  - Williams ME
AD  - University of Virginia School of Medicine, Charlottesville, VA;
FAU - Barrientos, Jacqueline C
AU  - Barrientos JC
AD  - Hofstra North Shore-Long Island Jewish School of Medicine, Hempstead, NY;
FAU - Chmielowska, Ewa
AU  - Chmielowska E
AD  - Oddzial Kliniczny Onkologii, Centrum Onkologii, Bydgoszcz, Poland;
FAU - Radford, John
AU  - Radford J
AD  - The University of Manchester and the Christie NHS Foundation Trust, Manchester, 
      United Kingdom;
FAU - Stilgenbauer, Stephan
AU  - Stilgenbauer S
AD  - Universitatsklinikum Ulm, Klinik fur Innere Medizin II, Ulm, Germany;
FAU - Dreyling, Martin
AU  - Dreyling M
AD  - University Hospital LMU Munich, Germany;
FAU - Jedrzejczak, Wieslaw Wiktor
AU  - Jedrzejczak WW
AD  - Medical University of Warsaw, Warsaw, Poland;
FAU - Johnson, Peter
AU  - Johnson P
AD  - Cancer Research UK Clinical Centre, Southampton General Hospital, Southampton, 
      United Kingdom;
FAU - Spurgeon, Stephen E
AU  - Spurgeon SE
AD  - Oregon Health and Science University, Portland, OR;
FAU - Zhang, Liang
AU  - Zhang L
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX;
FAU - Baher, Linda
AU  - Baher L
AD  - Pharmacyclics LLC, Sunnyvale, CA; and.
FAU - Cheng, Mei
AU  - Cheng M
AD  - Pharmacyclics LLC, Sunnyvale, CA; and.
FAU - Lee, Dana
AU  - Lee D
AD  - Pharmacyclics LLC, Sunnyvale, CA; and.
FAU - Beaupre, Darrin M
AU  - Beaupre DM
AD  - Pharmacyclics LLC, Sunnyvale, CA; and.
FAU - Rule, Simon
AU  - Rule S
AD  - Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United 
      Kingdom.
LA  - eng
SI  - ClinicalTrials.gov/NCT01236391
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - UL1 TR000427/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20150609
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Agammaglobulinaemia Tyrosine Kinase
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*administration & dosage/adverse effects
MH  - Diarrhea/chemically induced/physiopathology
MH  - Drug Administration Schedule
MH  - Dyspnea/chemically induced/physiopathology
MH  - Fatigue/chemically induced/physiopathology
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Lymphoma, Mantle-Cell/*drug therapy/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Nausea/chemically induced/physiopathology
MH  - Neutropenia/chemically induced/physiopathology
MH  - Protein Kinase Inhibitors/*administration & dosage/adverse effects
MH  - Protein-Tyrosine Kinases/*administration & dosage/adverse effects
MH  - Recurrence
MH  - Survival Analysis
MH  - Thrombocytopenia/chemically induced/physiopathology
MH  - Treatment Outcome
PMC - PMC4528064
EDAT- 2015/06/11 06:00
MHDA- 2015/10/28 06:00
PMCR- 2015/08/06
CRDT- 2015/06/11 06:00
PHST- 2015/03/18 00:00 [received]
PHST- 2015/05/26 00:00 [accepted]
PHST- 2015/06/11 06:00 [entrez]
PHST- 2015/06/11 06:00 [pubmed]
PHST- 2015/10/28 06:00 [medline]
PHST- 2015/08/06 00:00 [pmc-release]
AID - S0006-4971(20)30634-0 [pii]
AID - 2015/635326 [pii]
AID - 10.1182/blood-2015-03-635326 [doi]
PST - ppublish
SO  - Blood. 2015 Aug 6;126(6):739-45. doi: 10.1182/blood-2015-03-635326. Epub 2015 Jun 
      9.